The purposes of this research proposal are to advance the basic knowledge we have about the mechanisms of osseous repair following injury and to study how orthopaedic modes of therapy effect the biological repair process: a. Development of animal models for studying the molecular biology of normal fracture healing. b. Correlation of the biochemical events within the fracture callus with the histological staging and tissue types of normal fracture healing. c. Determine the effect of apposition, alignment, immobilization, and mode of internal fixation on the molecular biology of fracture healing. d. Determine the effect of altered hormonal and nutritional environment on the molecular biology of fracture healing. e. Characterization of the biological events in delayed union and pseudarthrosis. Current orthopaedic approaches to osseous injury, which have been developed from clinical experience and histological characterization of skeletal injury, do not consistently result in adequate fracture healing. The utilization of recently developed methodology for study in the metabolism of skeletal tissues should permit the characterization of the critical molecular events during fracture repair (methods including callus explant culture, collagen chromatography, electrophoresis, isotopic turnover, and matrix analysis all correlated with the histologic, radiographic, and biomechanical staging of fracture repair). An understanding of the biological mechanisms of osseous repair following fracture would identify the critical molecular events necessary for achieving successful osseous union.